Effect of age on the pharmacokinetics of a single daily dose of gentamicin sulfate in healthy foals.

摘要

Reasons for performing study: Therapeutic drug monitoring in a small number of foals of various ages indicates that the standard adult dose of 6.6 mg/kg bwt q. 24 h for gentamicin is too lowand a dose of 12 mg/kg bwt has been proposed. The pharmacokinetics of this dosage in foals and the ages at which this higher dose should be used have not previously been investigated. Objective: To determine the effect of age on the pharmacokinetics of a single 12 mg/kg bwt i.v. dose of gentamicin in foals. Methods: Six healthy foals were given a single i.v. dose of gentamicin at 1-3 days, 2, 4, 8 and 12 weeks of age. Plasma concentrations were measured using LC-MS/MS. Results: Elimination half-life (mean+or-s.d.) was significantly longer in 1-3-day-old foals (8.2+or-2.0 h) than in foals 4 weeks of age (3.7+or-1.5 h) or older. Volume of distribution was significantly higher in 1-3-day-old foals (0.75+or-0.20 l/kg bwt) than in 8- (0.27+or-0.10 l/kg bwt) or 12-week-old foals (0.29+or-0.11 l/kg bwt). Concentrations of gentamicin 1 h after administration were significantly lower in 1-3-day-old foals (20.52+or-2.07 micro g/ml) than in all other age groups (>42.16+or-17.57 micro g/ml). Concentrations of gentamicin 24 h after administration were significantly higher in the 1-3-day-old foals (1.97+or-0.90 micro g/ml) than in all the other age groups (<0.85+or-0.46 micro g/ml). Conclusions: The pharmacokinetics of gentamicin change considerably in the first 2 weeks of life. Potential relevance: Intravenous administration of gentamicin at a dose of 12 mg/kg bwt q. 36 h would be required in foals less than 2 weeks of age. In foals 2 weeks of age or older, a lower dose of 6.6 mg/kg bwt given q. 24 h was predicted to be adequate.